© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Chronic dermal lesions, such as pressure ulcers, are difficult to heal. Degradable tissue scaffold systems can be employed to serve as a provisional matrix for cellular ingrowth and facilitate regenerative healing during degradation. Degradable regenerative tissue scaffold matrices can be created by crosslinking albumin with functionalized poly(ethylene glycol) (PEG) polymers. The purpose of this study was to evaluate the stability of PEG-albumin scaffold systems formed using PEG polymers with three different functionalized end chemistries by quantifying in vitro system swellability to determine the most promising PEG crosslinking polymer for wound healing applications. Of the three polymers evaluated, PEG-succinimidyl glutarate (SG) exhibited consistent gelation and handling characteristics when used as the crosslinking agent with albumin. PEG-SG polymers were identified as an appropriate synthetic crosslinking moiety in a PEG-albumin scaffold system, and further in vitro and in vivo evaluation of this scaffold system is merited.